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Iñaki Izquierdo - One of the best experts on this subject based on the ideXlab platform.
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Rupatadine oral solution titration by body weight in paediatric patients suffering from allergic rhinitis a population pharmacokinetic study
Clinical Pharmacology: Advances and Applications, 2021Co-Authors: Eva Santamaria, Iñaki Izquierdo, Marta ValleAbstract:Background Allergic rhinitis (AR) and chronic urticaria, both are treated in children with doses of second generation of antihistamines that have been mostly based on extrapolation of data obtained in adults. The objectives of this work were to develop a model to explain the pharmacokinetics (PK) of Rupatadine, a second generation antihistamine, administered to children 2-11 years old and to calculate the non-compartmental PK parameters for two groups of age (2-5 and 6-11 years old) based on the individual Bayesian estimates from the selected model. Methods Data from two PK studies with Rupatadine oral solution (1 mg/mL) were pooled: Study A, an extensive blood sampling study performed in 11 children (6-11 years old) who received a single oral dose of Rupatadine; and Study B, a sparse blood sampling study in 40 children (2-5 years old) receiving multiple oral doses. A simultaneous population PK model was developed using data available for all children. Using individual Bayesian estimates from the selected model, steady-state plasma concentrations for both studies were simulated and the non-parametric PK parameters were calculated for two age groups: 2-5 years (subgroup I) and 6-11 years (subgroup II). Results A two-compartment model with first-order absorption and elimination with clearance depending on body weight, better described the PK of Rupatadine for 2-11 year old children. The plasma clearance dependence on weight was linear. The mean (SD) non-compartment PK parameters calculated using simulated plasma profiles at steady state were: Cmax, 2.54 (1.26) vs 1.96 (0.52) ng/mL; AUC0-24h, 10.74 (3.09) vs 10.38 (4.31) ng/mL/h; and t1/2, 12.28 (3.09) vs 15.94 (4.09) h, for children 6-11 and 2-5 years old, respectively. Conclusions The PK of Rupatadine depends on the weight of paediatric patients but not on their age. The dosage strategy adjusted by body weight in children 2-11 years old (2.5 mL if weight 10-25 kg, and 5 mL if ≥ 25 kg) provides similar exposure between the two groups of age, and to that obtained in adults with the 10 mg dose tablet formulation.
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higher efficacy of Rupatadine 20 mg and 10 mg versus placebo in patients with perennial allergic rhinitis a pooled responder analysis
Allergy Asthma & Clinical Immunology, 2020Co-Authors: Antonio Valero, Iñaki Izquierdo, Marek L Kowalski, Glenis K Scadding, Jean Bousquet, Joaquim MullolAbstract:The clinical efficacy of Rupatadine in terms of responders has not been previously explored in perennial allergic rhinitis (PAR). This pooled analysis included data from 6 randomised, double-blind, placebo-controlled trials conducted in PAR patients treated with Rupatadine 10 mg or 20 mg, or placebo. Participants were aged ≥ 18 years, with diagnosis of PAR and a Total 4 Nasal Symptom Score (T4NSS) ≥ 5. We evaluated the T4NSS and Total 5 Symptom Score (T5SS) for 28 days of treatment, the responder proportion (50% and 75% response), and the time to response. Efficacy data from 1486 patients were analysed: 585 received placebo, 682 Rupatadine 10 mg, and 219 Rupatadine 20 mg. Compared with placebo, Rupatadine promoted greater symptom improvements and higher responder proportions (50% and 75% response) for T4NSS and T5SS over 28 days. Symptom improvements and responder proportions were higher in the Rupatadine 20 mg group vs the 10 mg group. The time to response was shorter in the Rupatadine 20 mg group vs the 10 mg group for T4NSS (16 and 9 days for the 50% and 75% responses, respectively) and for T5SS (13 and 8 days for the 50% and 75% responses, respectively). Rupatadine was efficacious in reducing allergic rhinitis symptoms, showing high responder proportions. The faster and stronger effect of Rupatadine 20 mg may suggest its use in patients with severe PAR or not responding to the standard dose.
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Clinically relevant effect of Rupatadine 20 mg and 10 mg in seasonal allergic rhinitis: a pooled responder analysis
Clinical and Translational Allergy, 2019Co-Authors: Joaquim Mullol, Iñaki Izquierdo, Jean Bousquet, Kimihiro Okubo, Giorgio Walter Canonica, Antonio ValeroAbstract:Background: Different clinical trials showed the superior efficacy of Rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. Methods: This study is a pooled analysis of data of seven randomized, double-blind, placebo-controlled SAR studies comparing responder proportions upon treatment with Rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near-to-complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Results: Data from 1470 patients were analyzed: 332 treated with placebo, 662 with Rupatadine 10 mg and 476 with Rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in Rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in Rupatadine groups compared to the placebo group across the visits. Among Rupatadine-treated patients, those receiving 20 mg compared favourably for both cut-off responses. The time to achieve a proportion of responders was shorter in the Rupatadine 20 mg group than in the Rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near-to-complete response for both symptom scores was higher in Rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. Conclusions: This responder analysis confirms the superior efficacy of Rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose-dependent manner, with faster and higher response rates in the 20 mg group.
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clinically relevant effect of Rupatadine 20 mg and 10 mg in seasonal allergic rhinitis a pooled responder analysis
Clinical and Translational Allergy, 2019Co-Authors: Joaquim Mullol, Iñaki Izquierdo, Jean Bousquet, Kimihiro Okubo, Giorgio Walter Canonica, Antonio ValeroAbstract:Different clinical trials showed the superior efficacy of Rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. This study is a pooled analysis of data of seven randomized, double-blind, placebo-controlled SAR studies comparing responder proportions upon treatment with Rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near-to-complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Data from 1470 patients were analyzed: 332 treated with placebo, 662 with Rupatadine 10 mg and 476 with Rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in Rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in Rupatadine groups compared to the placebo group across the visits. Among Rupatadine-treated patients, those receiving 20 mg compared favourably for both cut-off responses. The time to achieve a proportion of responders was shorter in the Rupatadine 20 mg group than in the Rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near-to-complete response for both symptom scores was higher in Rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. This responder analysis confirms the superior efficacy of Rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose-dependent manner, with faster and higher response rates in the 20 mg group.
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Rupatadine oral solution for 2 5 year old children with allergic rhinitis a safety open label prospective study
Journal of Asthma and Allergy, 2018Co-Authors: Eva Santamaria, Iñaki Izquierdo, Jan Vermeulen, Marta Valle, Paul PotterAbstract:Background There are few clinical trials that assess the efficacy of antihistamines in very young children. Rupatadine is a second-generation antihistamine indicated for the treatment of allergic rhinitis (AR) and urticaria. In this study, AR symptoms were evaluated before and after daily 1 mg/mL Rupatadine oral solution administration in 2-5-year-old children. Methods A multicenter open-label study was carried out in 2-5-year-old children with AR. Safety assessments were collected during the study including spontaneous adverse events, vital signs, and electrocardiogram (QTc interval). Additionally, evaluations of Total Five Symptoms Score (T5SS, including: nasal congestion; sneezing; rhinorrhoea; itchy nose, mouth, throat, and/or ears; and itchy, watery, and red eyes) were analyzed. Symptoms were evaluated by parents/legal guardian before and after 4 weeks of Rupatadine administration, dosed according to body weight. Results A total of 44 children received the study treatment. Only 15 adverse events were reported. All of them were of mild intensity and considered not related to the study treatment. No patient exceeded the standard parameter of >450 ms in the last visit, for the QTc interval on their electrocardiograms. From a maximum score value of 15, T5SS values at Day 14 (6.35) and Day 28 (5.42) were both statistically significant different (p<0.001) from the baseline T5SS value (mean 8.65), with a reduction of 26.6% and 37.4%, respectively. All individual symptoms, including nasal congestion, showed also a decrease from baseline at both 14 and 28 days. Conclusion Rupatadine 1 mg/mL oral solution was found to be safe in 2-5-year-old children, correlating with an improvement of AR symptoms, overall and each individually, after a daily dose administration. With this study, we enlarge the available information in this very young pediatric patients' group, in which there is a general lack of clinical evidence.
Marcus Maurer - One of the best experts on this subject based on the ideXlab platform.
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Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2 11 years
Pediatric Allergy and Immunology, 2016Co-Authors: Paul Potter, Iñaki Izquierdo, Eva Santamaria, Essack Mitha, Laszlo Barkai, Gyorgyi Mezei, Marcus MaurerAbstract:Background Recommendations in current guidelines for the treatment of chronic spontaneous urticaria (CSU) in infants and children are mostly based on extrapolation of data obtained in adults. This study reports the efficacy and safety of Rupatadine, a modern H1 and PAF antagonist recently authorized in Europe for children with allergic rhinitis and CSU. Methods A double-blind, randomized, parallel-group, multicentre, placebo-controlled compared study to desloratadine was carried out in children aged 2–11 years with CSU, with or without angio-oedema. Patients received either Rupatadine (1 mg/ml), or desloratadine (0.5 mg/ml) or placebo once daily over 6 weeks. A modified 7-day cumulative Urticaria Activity Score (UAS7) was employed as the primary end-point. Results The absolute change of UAS7 at 42 days showed statistically significant differences between active treatments vs. placebo (−5.5 ± 7.5 placebo, −11.8 ± 8.7 Rupatadine and −10.6 ± 9.6 desloratadine; p < 0.001) and without differences between antihistamines compounds. There was a 55.8% decrease for Rupatadine followed by desloratadine (−48.4%) and placebo (−30.3%). Rupatadine but not desloratadine was statistically superior to placebo in reduction of pruritus (−57%). Active treatments also showed a statistically better improvement in children's quality of life compared to placebo. Adverse events were uncommon and non-serious in both active groups. Conclusion Rupatadine is effective and well tolerated in the relief of urticaria symptoms, improving quality of life over 6 weeks in children with CSU. This is the first study using a modified UAS to assess severity and efficacy outcome in CSU in children.
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Rupatadine 20 mg and 40 mg are effective in reducing the symptoms of chronic cold urticaria
Acta Dermato-venereologica, 2016Co-Authors: M Abajian, Iñaki Izquierdo, Laia Curtobarredo, Karoline Krause, Eva Santamaria, Martin K Church, Marcus Maurer, Ana GimenezarnauAbstract:Chronic cold urticaria (ColdU) is a rare disease characterized by mast cell-mediated wheals and angioedema following cold exposure. Second-generation H1-antihistamines, such as Rupatadine, are the recommended first-line therapy. As of yet, the effects of Rupatadine up-dosing on development of ColdU symptom have only been partially characterized. Two-centre, randomized, double-blind, 3-way crossover, placebo-controlled study in patients with a confirmed ColdU was designed to assess the effects of up-dosing of Rupatadine. A total of 23 patients were randomized to receive placebo, Rupatadine 20 mg/day, and Rupatadine 40 mg/day for 1 week. The primary outcome was change in critical temperature thresholds and critical stimulation time thresholds after treatment. Secondary endpoints included assessment of safety and tolerability of Rupatadine. Both 20 and 40 mg Rupatadine were highly effective in reducing critical temperature thresholds (p < 0.001) and critical stimulation time thresholds (p < 0.001). In conclusion, Rupatadine 20 and 40 mg significantly reduced the development of chronic cold urticaria symptom without an increase in adverse effects.
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Rupatadine in established treatment schemes improves chronic spontaneous urticaria symptoms and patients quality of life a prospective non interventional trial
Dermatologic Therapy, 2015Co-Authors: Martin Metz, Iñaki Izquierdo, Karsten Weller, Claudia Neumeister, Rolfhasso Bodeker, Ulrich Schwantes, Marcus MaurerAbstract:Introduction Chronic spontaneous urticaria (CSU) is a common and hard to treat condition associated with a substantial negative impact on patients’ quality of life (QoL). Clinical studies have shown that Rupatadine is effective and safe in the treatment of CSU, but data from routine clinical care are scarce. Therefore, we assessed the effectiveness and tolerability of Rupatadine in established dosages on CSU activity and patients’ QoL in a routine daily practice setting.
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o10 Rupatadine is effective and safe in the treatment of chronic spontaneous urticaria csu in pediatric patients 2 11 years old
Clinical and Translational Allergy, 2014Co-Authors: Paul Potter, Iñaki Izquierdo, Eva Santamaria, Essack Mitha, Laszlo Barkai, Alejandro Domenech, Josep Giralt, Marcus MaurerAbstract:Background Rupatadine is an anti-H1/PAF antagonist that has proven to be effective and safe in adults/adolescents for Allergic Rhinitis (AR) and Urticaria. In addition, Rupatadine has been recently licensed for the symptomatic treatment of AR in children aged 6-11 years. The aim of this study was to assess the efficacy and safety of Rupatadine oral solution in children with Chronic Spontaneous Urticaria (CSU).
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Rupatadine improves quality of life in mastocytosis a randomized double blind placebo controlled trial
Allergy, 2013Co-Authors: Frank Siebenhaar, Karoline Krause, Martin K Church, Martin Metz, Karsten Weller, A Fortsch, Markus Magerl, Peter Martus, Marcus MaurerAbstract:Background Mastocytosis is frequently associated with mast cell-mediated symptoms which require relieving medication. While second generation antihistamines (sgAHs) are the first line therapeutic strategy to treat mast cell mediator-related symptoms, controlled clinical trials on how they improve quality of life have not been performed. Methods This randomized, double-blind, placebo-controlled, cross-over trial assessed Rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale (VAS) and symptom specific quality of life questionnaire (ItchyQoL). Results The mean ItchyQoL total score and VAS symptom score were significantly improved in the Rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms. Conclusions In this first comprehensive trial of a sgAH in mastocytosis, Rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life.
Hiroshi Aoki - One of the best experts on this subject based on the ideXlab platform.
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usefulness of Rupatadine for pruritus of patients with atopic dermatitis
Arerugī (Allergy), 2020Co-Authors: Michihiro Hide, Takamasa Suzuki, Ayaka Tanaka, Kazuya Hirata, Naruyasu Komorita, Hajime Kubo, Hiroshi AokiAbstract:Background Histamine H1 receptor antagonists (antihistamines) are recommended as adjunctive therapy for atopic dermatitis (AD). However, their long-term usefulness and the effect of updosing have not been clarified. Purpose To analyzed the long-term usefulness and the effect of updosing of Rupatadine, a second generation antihistamine, for patients with AD. Methods Efficacy and safety of Rupatadine were evaluated in 66 AD patients, including 50 patients with dose escalation by post hoc analysis of the phase III trial of Rupatadine for Japanese patients with pruritus associated with skin diseases. Results The mean score at baseline total pruritus score (TPS) was 4.682. It decreased to 3.885 at 2 weeks, and 2.376 at 52 weeks by Rupatadine administration. The change (of one week after baseline TPS) was significant. Baseline TPS of dose escalation groups, either after 2 weeks or after week 4, were higher than those of 10mg maintenance dose cases, but no significant difference was shown in the change from baseline TPS among the groups at 52 weeks. The occurrence of adverse drug reactions and somnolence were observed in 19.7% and 15.2% of the subjects. Conclusion These results suggest the long-term usefulness of Rupatadine for pruritus in AD.
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long term safety and efficacy of Rupatadine in japanese patients with itching due to chronic spontaneous urticaria dermatitis or pruritus a 12 month multicenter open label clinical trial
Journal of Dermatological Science, 2019Co-Authors: Michihiro Hide, Takamasa Suzuki, Ayaka Tanaka, Hiroshi AokiAbstract:Abstract Background Rupatadine is a novel H1 antihistamine with platelet-activating factor antagonist activity. Its efficacy and safety on pruritic skin diseases have been demonstrated by 10 mg/day Rupatadine in a two weeks clinical trial. Objective To investigate the long-term efficacy and safety of Rupatadine in the management of pruritus, and the clinical effect of updosing to 20 mg in Japanese adult and adolescent patients. Methods In this 52-week, multicenter, open-label clinical trial (JapicCTI-152787), 206 patients (132, eczema or dermatitis; 58, pruritus; and 16, chronic spontaneous urticaria) received the study medication. The primary efficacy endpoint was change from baseline in the total pruritus score to Week 2 by treatment with Rupatadine 10 mg once daily. From Week 3 to Week 52, Rupatadine updosing to 20 mg was allowed. Results The mean [95% CI] change from baseline to Week 2 in the total pruritus score was −1.241 [−1.450, −1.033] (paired t test, P Conclusions This clinical trial demonstrated the short- and long-term benefits of Rupatadine in the management of patients with chronic spontaneous urticaria, dermatitis, and pruritus. Rupatadine 10 and 20 mg doses are effective for the treatment of itch in adults and adolescents, and can be used safely on a long-term basis.
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efficacy and safety of Rupatadine in japanese patients with seasonal allergic rhinitis a double blind randomized multicenter placebo controlled clinical trial
Allergology International, 2019Co-Authors: Kimihiro Okubo, Takamasa Suzuki, Ayaka Tanaka, Hiroshi AokiAbstract:Abstract Background Rupatadine is a novel non-sedating second-generation H1-antihistamine with antiplatelet-activating factor activity, first marketed in Spain in 2003. It is used for treating allergic rhinitis in more than 80 countries. This study investigated its efficacy and safety in Japanese patients with seasonal allergic rhinitis (SAR). Methods This was a randomized, placebo-controlled, double-blind study conducted at 4 medical institutions in Japan (JapicCTI-152785). Adolescent and adult SAR outpatients aged 12–64 years entered a 1-week placebo run-in period. After eligibility was confirmed, patients orally received placebo, Rupatadine 10 mg, or 20 mg once daily for 2 weeks. The primary endpoint was a change from baseline to second week of treatment in total 4 nasal symptom score (T4NSS). Results Nine hundred patients were randomly assigned to placebo, Rupatadine 10 mg, or Rupatadine 20 mg (302, 298, and 300 patients, respectively). The least squares mean difference in the primary endpoint between Rupatadine and placebo was −1.085 for 10 mg, and −1.415 for 20 mg (analysis of covariance, both P Conclusions Rupatadine 10 and 20 mg were significantly superior to placebo in improving nasal and ocular symptoms of SAR, and were well tolerated.
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efficacy and safety of Rupatadine in japanese adult and adolescent patients with chronic spontaneous urticaria a double blind randomized multicenter placebo controlled clinical trial
Allergology International, 2019Co-Authors: Michihiro Hide, Takamasa Suzuki, Ayaka Tanaka, Hiroshi AokiAbstract:Abstract Background Rupatadine, a novel nonsedating second-generation H1-antihistamine with antiplatelet-activating factor activity, has been used in the treatment of allergic rhinitis and urticaria in European countries since 2003. However, its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU) are unknown. Methods We conducted a prospective, multicenter, randomized, placebo-controlled, double-blind study in adolescent and adult CSU outpatients aged 12 to Results The results yielded a least squares mean TPS difference of −1.956 between Rupatadine 10 mg versus placebo, and −2.121 between Rupatadine 20 mg versus placebo (analysis of covariance, both P Conclusions The primary and secondary efficacy endpoints consistently favored Rupatadine 10 and 20 mg doses over the placebo. No noteworthy dose-related increase in the incidence of adverse drug reactions was observed. Rupatadine is safe and effective at a dose of 10 mg once daily, and can be safely increased to 20 mg once daily, as necessary.
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Efficacy and safety of Rupatadine in Japanese patients with seasonal allergic rhinitis: A double-blind, randomized, multicenter, placebo-controlled clinical trial
'Elsevier BV', 2019Co-Authors: Kimihiro Okubo, Takamasa Suzuki, Ayaka Tanaka, Hiroshi AokiAbstract:Background: Rupatadine is a novel non-sedating second-generation H1-antihistamine with antiplatelet-activating factor activity, first marketed in Spain in 2003. It is used for treating allergic rhinitis in more than 80 countries. This study investigated its efficacy and safety in Japanese patients with seasonal allergic rhinitis (SAR). Methods: This was a randomized, placebo-controlled, double-blind study conducted at 4 medical institutions in Japan (JapicCTI-152785). Adolescent and adult SAR outpatients aged 12–64 years entered a 1-week placebo run-in period. After eligibility was confirmed, patients orally received placebo, Rupatadine 10 mg, or 20 mg once daily for 2 weeks. The primary endpoint was a change from baseline to second week of treatment in total 4 nasal symptom score (T4NSS). Results: Nine hundred patients were randomly assigned to placebo, Rupatadine 10 mg, or Rupatadine 20 mg (302, 298, and 300 patients, respectively). The least squares mean difference in the primary endpoint between Rupatadine and placebo was −1.085 for 10 mg, and −1.415 for 20 mg (analysis of covariance, both P
Ana Gimenezarnau - One of the best experts on this subject based on the ideXlab platform.
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Rupatadine 20 mg and 40 mg are effective in reducing the symptoms of chronic cold urticaria
Acta Dermato-venereologica, 2016Co-Authors: M Abajian, Iñaki Izquierdo, Laia Curtobarredo, Karoline Krause, Eva Santamaria, Martin K Church, Marcus Maurer, Ana GimenezarnauAbstract:Chronic cold urticaria (ColdU) is a rare disease characterized by mast cell-mediated wheals and angioedema following cold exposure. Second-generation H1-antihistamines, such as Rupatadine, are the recommended first-line therapy. As of yet, the effects of Rupatadine up-dosing on development of ColdU symptom have only been partially characterized. Two-centre, randomized, double-blind, 3-way crossover, placebo-controlled study in patients with a confirmed ColdU was designed to assess the effects of up-dosing of Rupatadine. A total of 23 patients were randomized to receive placebo, Rupatadine 20 mg/day, and Rupatadine 40 mg/day for 1 week. The primary outcome was change in critical temperature thresholds and critical stimulation time thresholds after treatment. Secondary endpoints included assessment of safety and tolerability of Rupatadine. Both 20 and 40 mg Rupatadine were highly effective in reducing critical temperature thresholds (p < 0.001) and critical stimulation time thresholds (p < 0.001). In conclusion, Rupatadine 20 and 40 mg significantly reduced the development of chronic cold urticaria symptom without an increase in adverse effects.
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Rupatadine and its effects on symptom control stimulation time and temperature thresholds in patients with acquired cold urticaria
Annals of Allergy Asthma & Immunology, 2010Co-Authors: Martin Metz, Iñaki Izquierdo, Ana Gimenezarnau, Elisabeth Scholz, Marta Ferran, Marcus MaurerAbstract:Background Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a dual antagonist of both histamine and platelet-activating factor. Objective To assess Rupatadine efficacy in preventing reactions to cold challenge in patients with ACU. Methods A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received Rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (Temp Test 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge. Results After Rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and Temp Test 3.0 challenge ( P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold ( P P = .01), pruritus ( P = .005), burning sensation ( P = .03), and subjective complaints ( P = .03) after Rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment. Conclusion Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms.
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the use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo controlled treatment with Rupatadine 10 and 20 mg
Journal of The European Academy of Dermatology and Venereology, 2009Co-Authors: Ana Gimenezarnau, Iñaki Izquierdo, Marcus MaurerAbstract:Background According to the EAACI/GA 2 LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated Rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed. Methods This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with Rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS). Results A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of Rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with Rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than Rupatadine 10 mg. Conclusion Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.
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Rupatadine in allergic rhinitis and chronic urticaria
Allergy, 2008Co-Authors: J Mullol, Marcus Maurer, Ana Gimenezarnau, Cesar Picado, Jean Bousquet, M.l. Kowalski, Claus Bachert, E Martiguadano, Walter Canonica, G. ScaddingAbstract:Histamine is the primary mediator involved the pathophysiology of allergic rhinitis and chronic urticaria, and this explains the prominent role that histamine H-1-receptor antagonists have in the treatment of these disorders. However, histamine is clearly not the only mediator involved in the inflammatory cascade. There is an emerging view that drugs which can inhibit a broader range of inflammatory processes may prove to be more effective in providing symptomatic relief in both allergic rhinitis and chronic urticaria. This is an important consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative which provides a scientific basis for defining what are the desirable properties of an 'ideal' antihistamine. In this review of Rupatadine, a newer dual inhibitor of histamine H-1- and PAF-receptors, we evaluate the evidence for a mechanism of action which includes anti-inflammatory effects in addition to a powerful inhibition of H-1- and PAF-receptors. We assess this in relation to the clinical efficacy (particularly the speed of onset of action) and safety of Rupatadine, and importantly its longer term utility in everyday life. In clinical trials, Rupatadine has been shown to be an effective and well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once-daily administration. In comparative clinical trials Rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis. Importantly, Rupatadine demonstrated no adverse cardiovascular effects in preclinical or extensive clinical testing, nor negative significant effects on cognition or psychomotor performance (including a practical driving study). It improved the overall well-being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, Rupatadine is a recently introduced dual inhibitor of histamine H-1- and PAF-receptors, which has been shown to be an effective and generally well-tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti-inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early- and late-phase inflammatory response, but the clinical relevance of these effects remain to be clarified.
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Rupatadine in the treatment of chronic idiopathic urticaria a double blind randomized placebo controlled multicentre study
Allergy, 2007Co-Authors: Ana Gimenezarnau, Iñaki Izquierdo, Ramon M Pujol, S Ianosi, A Kaszuba, A Malbran, G Poop, E Donado, I Perez, E ArnaizAbstract:Background: Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. Objective: To study Rupatadine efficacy and safety for moderate to severe CIU treatment. Methods: This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with Rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. Results: A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg Rupatadine, respectively, compared with placebo (44.9%). Both doses of Rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. Conclusion: Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU.
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Rupatadine oral solution titration by body weight in paediatric patients suffering from allergic rhinitis a population pharmacokinetic study
Clinical Pharmacology: Advances and Applications, 2021Co-Authors: Eva Santamaria, Iñaki Izquierdo, Marta ValleAbstract:Background Allergic rhinitis (AR) and chronic urticaria, both are treated in children with doses of second generation of antihistamines that have been mostly based on extrapolation of data obtained in adults. The objectives of this work were to develop a model to explain the pharmacokinetics (PK) of Rupatadine, a second generation antihistamine, administered to children 2-11 years old and to calculate the non-compartmental PK parameters for two groups of age (2-5 and 6-11 years old) based on the individual Bayesian estimates from the selected model. Methods Data from two PK studies with Rupatadine oral solution (1 mg/mL) were pooled: Study A, an extensive blood sampling study performed in 11 children (6-11 years old) who received a single oral dose of Rupatadine; and Study B, a sparse blood sampling study in 40 children (2-5 years old) receiving multiple oral doses. A simultaneous population PK model was developed using data available for all children. Using individual Bayesian estimates from the selected model, steady-state plasma concentrations for both studies were simulated and the non-parametric PK parameters were calculated for two age groups: 2-5 years (subgroup I) and 6-11 years (subgroup II). Results A two-compartment model with first-order absorption and elimination with clearance depending on body weight, better described the PK of Rupatadine for 2-11 year old children. The plasma clearance dependence on weight was linear. The mean (SD) non-compartment PK parameters calculated using simulated plasma profiles at steady state were: Cmax, 2.54 (1.26) vs 1.96 (0.52) ng/mL; AUC0-24h, 10.74 (3.09) vs 10.38 (4.31) ng/mL/h; and t1/2, 12.28 (3.09) vs 15.94 (4.09) h, for children 6-11 and 2-5 years old, respectively. Conclusions The PK of Rupatadine depends on the weight of paediatric patients but not on their age. The dosage strategy adjusted by body weight in children 2-11 years old (2.5 mL if weight 10-25 kg, and 5 mL if ≥ 25 kg) provides similar exposure between the two groups of age, and to that obtained in adults with the 10 mg dose tablet formulation.
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Rupatadine oral solution for 2 5 year old children with allergic rhinitis a safety open label prospective study
Journal of Asthma and Allergy, 2018Co-Authors: Eva Santamaria, Iñaki Izquierdo, Jan Vermeulen, Marta Valle, Paul PotterAbstract:Background There are few clinical trials that assess the efficacy of antihistamines in very young children. Rupatadine is a second-generation antihistamine indicated for the treatment of allergic rhinitis (AR) and urticaria. In this study, AR symptoms were evaluated before and after daily 1 mg/mL Rupatadine oral solution administration in 2-5-year-old children. Methods A multicenter open-label study was carried out in 2-5-year-old children with AR. Safety assessments were collected during the study including spontaneous adverse events, vital signs, and electrocardiogram (QTc interval). Additionally, evaluations of Total Five Symptoms Score (T5SS, including: nasal congestion; sneezing; rhinorrhoea; itchy nose, mouth, throat, and/or ears; and itchy, watery, and red eyes) were analyzed. Symptoms were evaluated by parents/legal guardian before and after 4 weeks of Rupatadine administration, dosed according to body weight. Results A total of 44 children received the study treatment. Only 15 adverse events were reported. All of them were of mild intensity and considered not related to the study treatment. No patient exceeded the standard parameter of >450 ms in the last visit, for the QTc interval on their electrocardiograms. From a maximum score value of 15, T5SS values at Day 14 (6.35) and Day 28 (5.42) were both statistically significant different (p<0.001) from the baseline T5SS value (mean 8.65), with a reduction of 26.6% and 37.4%, respectively. All individual symptoms, including nasal congestion, showed also a decrease from baseline at both 14 and 28 days. Conclusion Rupatadine 1 mg/mL oral solution was found to be safe in 2-5-year-old children, correlating with an improvement of AR symptoms, overall and each individually, after a daily dose administration. With this study, we enlarge the available information in this very young pediatric patients' group, in which there is a general lack of clinical evidence.
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Time profile of the observed plasma concentrations of Rupatadine in 6–11 year olds after the administration of 2.5-mg (crosses) or 5-mg (open circles) doses.
2017Co-Authors: Eva Santamaria, Iñaki Izquierdo, Javier Alejandro Estévez, Jordi Riba, Marta ValleAbstract:Left panel, observed concentrations of Rupatadine in log scale. Right panel, visual predictive check of the final selected model built with data for Rupatadine in 6–11 year olds. Solid thin lines cover the area including 90% percentile interval of the simulated plasma concentrations over time, and thick line represents the mean of the simulated profiles. Concentrations have been normalised to a 5-mg dose.
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pharmacokinetics safety and cognitive function profile of Rupatadine 10 20 and 40 mg in healthy japanese subjects a randomised placebo controlled trial
PLOS ONE, 2016Co-Authors: Jorg Taubel, Eva Santamaria, Georg Ferber, Sara Fernandes, Ulrike Lorch, Iñaki IzquierdoAbstract:Introduction Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of Rupatadine in healthy Japanese subjects after single and multiple oral doses. Methods In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating Rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of Rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP), reaction time (RT), spatial working memory (SWM) and visual analogue scales (VAS). Results Exposure to Rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10–40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs) or withdrawals due to treatment–emergent adverse events (TEAEs) in this study. The therapeutic dose of Rupatadine did not show any CNS impairment in any of the cognitive tests. Conclusions This study demonstrated that Rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with Rupatadine.
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Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2 11 years
Pediatric Allergy and Immunology, 2016Co-Authors: Paul Potter, Iñaki Izquierdo, Eva Santamaria, Essack Mitha, Laszlo Barkai, Gyorgyi Mezei, Marcus MaurerAbstract:Background Recommendations in current guidelines for the treatment of chronic spontaneous urticaria (CSU) in infants and children are mostly based on extrapolation of data obtained in adults. This study reports the efficacy and safety of Rupatadine, a modern H1 and PAF antagonist recently authorized in Europe for children with allergic rhinitis and CSU. Methods A double-blind, randomized, parallel-group, multicentre, placebo-controlled compared study to desloratadine was carried out in children aged 2–11 years with CSU, with or without angio-oedema. Patients received either Rupatadine (1 mg/ml), or desloratadine (0.5 mg/ml) or placebo once daily over 6 weeks. A modified 7-day cumulative Urticaria Activity Score (UAS7) was employed as the primary end-point. Results The absolute change of UAS7 at 42 days showed statistically significant differences between active treatments vs. placebo (−5.5 ± 7.5 placebo, −11.8 ± 8.7 Rupatadine and −10.6 ± 9.6 desloratadine; p < 0.001) and without differences between antihistamines compounds. There was a 55.8% decrease for Rupatadine followed by desloratadine (−48.4%) and placebo (−30.3%). Rupatadine but not desloratadine was statistically superior to placebo in reduction of pruritus (−57%). Active treatments also showed a statistically better improvement in children's quality of life compared to placebo. Adverse events were uncommon and non-serious in both active groups. Conclusion Rupatadine is effective and well tolerated in the relief of urticaria symptoms, improving quality of life over 6 weeks in children with CSU. This is the first study using a modified UAS to assess severity and efficacy outcome in CSU in children.
